Song Yanyan, Chen Song, Xiang Wei, Xiao Muran, Xiao Hui
Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Arch Med Sci. 2020 Nov 29;17(4):1056-1063. doi: 10.5114/aoms.2020.101305. eCollection 2021.
Multiple myeloma (MM) is a malignant hematologic tumor. Although many new drugs are currently found to significantly improve the median survival, MM is still not curable due partly to drug resistance recurrence. Epidemiological studies have shown that patients with type 2 diabetes have a high risk of malignancy, and patients' treatment with metformin could reduce the risk of cancer as well as associated mortality.
We used chemotherapeutics - melphalan combined with metformin or the single drug - to treat RPMI8226 cells and used a series of tests to detect the drug sensitivity, apoptotic rate, DNA damage and the concentration of ATP. SPSS 17.0 was used to analyze the data.
The inhibitory effect of melphalan on RPMI8226 cells was significantly increased after metformin was added ( < 0.05), and the inhibitory effect was enhanced with the increasing concentration of melphalan. The comet assay showed that metformin increased melphalan-induced DNA damage and increased the apoptotic rate from 12.7 ±2.8% to 18.8 ±1.5% ( < 0.05). In the ATP concentration test, the concentration of ATP in the tumor cells was significantly decreased from 0.42 ±0.01 μmol/l to 0.08 ±0.02 μmol/l ( < 0.05).
Metformin can promote DNA damage induced by melphalan and decrease the concentration of ATP in the process of repairing DNA damage to hinder the anti-apoptotic process of tumor cells, which showed the pesticide effect of the enhanced sensitivity of multiple myeloma cells to melphalan.
多发性骨髓瘤（MM）是一种恶性血液肿瘤。尽管目前发现许多新药可显著提高中位生存期，但MM仍无法治愈，部分原因是耐药性复发。流行病学研究表明，2型糖尿病患者患恶性肿瘤的风险较高，而患者使用二甲双胍治疗可降低患癌风险及相关死亡率。
我们使用化疗药物——美法仑联合二甲双胍或单一药物——来处理RPMI8226细胞，并使用一系列检测来检测药物敏感性、凋亡率、DNA损伤和ATP浓度。使用SPSS 17.0分析数据。
添加二甲双胍后，美法仑对RPMI8226细胞的抑制作用显著增强（<0.05），且随着美法仑浓度的增加抑制作用增强。彗星试验表明，二甲双胍增加了美法仑诱导的DNA损伤，并使凋亡率从12.7±2.8%提高到18.8±1.5%（<0.05）。在ATP浓度检测中，肿瘤细胞中的ATP浓度从0.42±0.01μmol/l显著降低至0.08±0.02μmol/l（<0.05）。
二甲双胍可促进美法仑诱导的DNA损伤，并在修复DNA损伤过程中降低ATP浓度，从而阻碍肿瘤细胞的抗凋亡过程，这显示了其增强多发性骨髓瘤细胞对美法仑敏感性的增效作用。
